Penicillin Allergy label - the unmet needs - causes and potential solutions.

Summary: Background. Penicillin allergy is the most prevalent drug allergy. Its overdiagnosis has been associated with inappropriate antibiotic prescribing, increased antimicrobial resistance, worse clinical outcomes, and increased healthcare costs. Methods. 403 inpatients were audited against National Institute of Clinical Excellence (NICE) Clinical Guidance 183 (CG183) on diagnosis, investigations, documentation, and management of penicillin allergy. 50 junior doctors were surveyed to explore barriers to best practice, investigating their knowledge of, and confidence using the NICE CG183 guidelines. Their views on potential solutions were also explored. Results. The audit identified: 13% (54/403) of patients labelled penicillin allergic; 24% (13/54) fulfilled criteria for referral but none were referred to specialists. With regards to documentation: 33% (18/54) documented exact drug name; 72% (39/54) documented signs and symptoms; 20% (11/54) documented reaction severity; 2% (1/54) documented indication for the drug taken; 4% (2/54) documented number of doses taken or days before onset of the reaction and 0% documented route of administration. The survey revealed barriers including: 1- lack of awareness and confidence in applying the NICE CG183 on diagnosis and management; 2- tendency to err on the side of caution when de-labelling patients. All agreed that decision support tools would address barriers to best practice and appropriate penicillin allergy de-labelling Conclusions.The current practice of diagnosing, documenting, and managing penicillin allergies does not meet NICE CG183. A lack of awareness and confidence using NICE CG183 are the main contributing barriers to best practice. Decision support tools, including a drug allergy app, would help overcome these barriers.

The psychological determinants of making lifestyle and dietary behaviours after using an online cognitive health tool and its associated recommendations for protective cognitive health behaviours

Background & objectives: The Covid-19 pandemic has revolutionised how we receive services, with a huge shift to online delivery. Online health promotion tools could be a cost-effective and safe way to improve population health. We used mixed methods to explore user responses to an online cognitive health tool.Methods15–28 months after completing an online tool, comprising a cognitive test, lifestyle questionnaire; and dietary and lifestyle behaviour feedback, 4826 participants completed an online survey about their perceptions of it; and questions about their capability, opportunity and motivation for behavioural change developed using the COM-B behaviour change model. We reported how responses to the behaviour change questionnaire predicted decisions to make lifestyle and dietary changes. 24 participants attended focus groups to further explore their responses.ResultsMost users reported that the tool was useful (88%), with 37% reporting they made lifestyle or dietary changes after using it. More positive responses to questions regarding capability and motivation predicted making changes. Over a third (36%) felt more fearful after completing the tool. In qualitative findings, we identified barriers to engagement across the three COM-B domains: a sense that information was “nothing new” (so did not enhance capability); that “experts don’t agree” and that the tool may not be credible (influencing motivation), and a lack of support from peers and lower availability of healthy food (reducing opportunities for change).ConclusionsFuture e-health tools will be most effective if they have high credibility, demonstrate advice is evidence-based and provide opportunities for support and follow up. (AU)

The addition of flexible endoscopic suturing to stenting for the management of transmural esophageal wall defects: a single tertiary center experience.

BACKGROUND AND AIMS: Endoscopic stenting is the standard of care for full thickness esophageal wall defects. The aim of this study is to evaluate outcomes of endoscopic closure of esophageal defects using stenting, with or without endoscopic suturing. METHODS: This is a single-center retrospective study of patients with esophageal wall defects who underwent endoscopic interventions. Outcomes of stenting with or without endoscopic suturing of the defect were assessed. Univariate and multivariate logistic regression models were used to examine factors associated with successful defect closure. RESULTS: One hundred and fourteen patients with esophageal wall defects underwent 254 endoscopies with an overall complete closure rate of 75.8%. Twenty-three (20.2%) patients underwent primary closure using endoscopic suturing and subsequent esophageal stenting, while 91 (79.8%) underwent esophageal stenting only. The dual modality group (versus the stent-only group) had similar defect closure rates (84.2 vs. 73.8%, p = 0.55) and time to stent migration (37 vs. 12.5 days, p = 0.07), but was associated with longer procedure times (60 vs. 36 min, p < 0.01) and fewer additional endoscopic procedures (13.6 vs. 43.2%, p = 0.01). Stent suturing significantly decreased migration (35.5 vs. 58.5%, p = 0.04), was associated with fewer additional endoscopies (15.4 vs. 50%, p < 0.01) and reduced need for additional stents (7.7 vs. 34.3%, p < 0.01). On multivariate analysis, chronic defects (> four weeks old) were 81% less likely to close compared to acute (≤ 4 weeks) defects (OR 0.19, CI 0.04-0.77, p = 0.02), and large diameter stents (23 mm) were associated with higher odds of defect closure (OR 3.36, CI 1.02-11.4, p = 0.04). CONCLUSION: Endoscopic treatment of esophageal wall defects is safe, effective, and more likely to be successful in acute defects using larger caliber stents. Stent suturing reduces migration, need for additional endoscopic procedures, and stent exchanges. Further comparative studies with larger cohorts are needed to validate our results.

Simulated future conditions of ocean warming and acidification disrupt the microbiome of the calcifying foraminifera Marginopora vertebralis across life stages.

Foraminifera host diverse microbial communities that can shift in response to changing environmental conditions. To characterize climate change impacts on the foraminifera microbiome across life stages, we exposed adult Marginopora vertebralis (Large Benthic Foraminifera) to pCO2 and temperature scenarios representing present-day, 2050 and 2100 levels and raised juveniles under present-day and 2050 conditions. While treatment condition had no significant effect on the seawater microbial communities, exposure to future scenarios significantly altered both adult and juvenile microbiomes. In adults, divergence between present-day and 2050 or 2100 conditions was primarily driven by a reduced relative abundance of Oxyphotobacteria under elevated temperature and pCO2 . In juveniles, the microbial shift predominantly resulted from changes in the proportion of Proteobacteria. Indicator species analysis identified numerous treatment-specific indicator taxa, most of which were indicative of present-day conditions. Oxyphotobacteria, previously reported as putative symbionts of foraminifera, were indicative of present-day and 2050 conditions in adults, but of present-day conditions only in juveniles. Overall, we show that the sensitivity of the M. vertebralis microbiome to climate change scenarios extends to both life stages and primarily correlates with declines in Oxyphotobacteria and shifts in Proteobacteria under elevated temperature and pCO2 .

Author Correction: Effects of larvae density and food concentration on Crown-of-Thorns seastar (Acanthaster cf. solaris) development in an automated flow-through system.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Effects of larvae density and food concentration on Crown-of-Thorns seastar (Acanthaster cf. solaris) development in an automated flow-through system.

Coral-eating Crown-of-Thorns Sea stars (Acanthaster spp.) are major contributors to coral reef loss in the Indo-Pacific region. A release from food limitation of their planktotrophic larvae through enhanced pelagic productivity is one of the main hypothesis explaining population outbreaks ('nutrient limitation hypothesis'). To improve the understanding of these outbreaks we developed an automated flow- through larvae rearing system that maintained food (microalgae) at set levels over the course of four 15d experiments. This resulted in stable food concentrations in experimental tanks. Increased algae concentrations had a significant positive effect on larval development and size at 10 and 15 days post fertilization (dpf). Larvae densities had no effect at 10 dpf. At 15 dpf greater larvae densities were associated with declines in larvae size. Larval development was slowed under higher larvae densities. Thus, the effects of algae concentration and larvae density were additive at 15 dpf, with larvae under low densities at a given algae concentration being further developed than those under higher densities. The development of a flow-through system gives greater insight into the effect of algae and larvae concentrations on Acanthaster development, and the system can be applied to further test the nutrient-limitation hypothesis for present and future outbreaks.

A case-control study of epidemiological factors associated with leptospirosis in South Gujarat region.

BACKGROUND: The current study was planned to identify the epidemiological factors associated with leptospirosis in South Gujarat region using neighborhood controls. METHODS: A total of 100 cases of leptospirosis occurred in South Gujarat region during the year 2012 were selected using simple random sampling. Three neighbors of the selected cases formed the controls (n = 300). A pretested structured questionnaire was used for data collection and data were analyzed using Epi Info 2007. RESULTS: There was significant association of illiteracy (odds ratio [OR] =1.82, 95% confidence interval [CI] =1.14-2.89), working in waterlogged fields during the reference season (OR = 4.6, 95% CI = 1.6-17.9), swimming/bathing in canals, open air defecation practices, storage of cow dung in or surrounding house, residence in the house made up of cow dung walls, households with access of food to rodents, injuries over hands/foot during the endemic season (OR = 3, 95% CI = 1.8-4.8), and history of skin disease during the endemic season (OR = 4.2, 95% CI = 2-8.5), with leptospirosis. Only 10% of individuals had gumboots for protection. A total of 83 (83%) cases and 240 (80%) controls had taken oral doxycycline chemoprophylaxis (P > 0.05). Cases had taken chemoprophylaxis for a median 4 weeks (range: 1-8) while controls had taken the same for median 8 weeks (range = 1-8) (P < 0.002). CONCLUSIONS: Although the commonly established factors appear to be associated with leptospirosis, the role of host factors seems to play a more important role in determining susceptibility to leptospirosis in exposed individuals.

Clinical significance of geographic miss when using conventional four field radiotherapy technique in treatment of locally advanced carcinoma cervix.

BACKGROUND: Although conventional four- field radiotherapy based on bony landmarks has been traditionally used, areas of geographical miss due to individual variation in pelvic anatomy have been identified with advanced imaging techniques. AIMS: The primary aim of this study is to evaluate the geographical miss in patientswhen using the conventional four-field planningplanning and to find out the impact of 3-D conformal CT based in patients with locally advanced carcinoma cervix. MATERIALS AND METHODS: In 50 patients, target volume delineation was done on planning computed tomography (CT) scans, according to guidelines by Taylor et al. Patients were treated with modified four field plan, except for the superior, where field border was kept at L4-L5 interspace A dosimetric comparison was done between the conventional four-field based on bony landmarks and the target volume delineated on computed tomography. The disease free survival, pelvic and para aortic nodal free survival, distant failures free survival were calculated using Kaplan Meir Product Limit Method. RESULTS: Patients were followed-up for a median period of 11 months. The median V95 for conventional and modified extended four field plans were 89.4% and 91.3% respectively. Patients with V95 for modified extended pelvic fields less than 91.3% had a trend toward inferior disease free survival (mean DFS 9.8 vs. 13.9 months) though the difference was not statistically significant log rank test. CONCLUSIONS: Our preliminary data shows trend toward lower DFS in patients with inadequate target volume coverage. We recommend routine use of CT based planning for four field technique.

Epigenetic Alteration by DNA Methylation of ESR1, MYOD1 and hTERT Gene Promoters is Useful for Prediction of Response in Patients of Locally Advanced Invasive Cervical Carcinoma Treated by Chemoradiation.

AIMS: Locally advanced invasive cervical cancer [International Federation of Gynecology and Obstetrics (FIGO) IIB/III] is treated by chemoradiation. The response to treatment is variable within a given FIGO stage. Therefore, the aim of the present study was to evaluate the gene promoter methylation profile and corresponding transcript expression of a panel of six genes to identify genes which could predict the response of patients treated by chemoradiation. MATERIALS AND METHODS: In total, 100 patients with invasive cervical cancer in FIGO stage IIB/III who underwent chemoradiation treatment were evaluated. Ten patients developed systemic metastases during therapy and were excluded. On the basis of patient follow-up, 69 patients were chemoradiation-sensitive, whereas 21 were chemoradiation-resistant. Gene promoter methylation and gene expression was determined by TaqMan assay and quantitative real-time PCR, respectively, in tissue samples. RESULTS: The methylation frequency of ESR1, BRCA1, RASSF1A, MLH1, MYOD1 and hTERT genes ranged from 40 to 70%. Univariate and hierarchical cluster analysis revealed that gene promoter methylation of MYOD1, ESR1 and hTERT could predict for chemoradiation response. A pattern of unmethylated MYOD1, unmethylated ESR1 and methylated hTERT promoter as well as lower ESR1 transcript levels predicted for chemoradiation resistance. CONCLUSION: Methylation profiling of a panel of three genes that includes MYOD1, ESR1 and hTERT may be useful to predict the response of invasive cervical carcinoma patients treated with standard chemoradiation therapy.

Bladder-Rectum Spacer Balloon versus Vaginal Gauze Packing in High Dose Rate Brachytherapy in Cervical Cancer: A Randomised Study. Part II.

AIMS: To compare the inter-fraction dose variation for bladder and rectum using a bladder-rectum spacer balloon (BRSB) versus vaginal gauze packing (VGP) in patients treated with high dose rate intracavitary brachytherapy for carcinoma cervix. MATERIALS AND METHODS: After the completion of external radiotherapy, 80 patients were randomised to receive intracavitary brachytherapy using either the BRSB or VGP. The procedure was carried out under general anaesthesia using tandem ovoid applicators. Computed tomography-based planning was carried out and the dose was prescribed to point A. Doses to 0.1, 1 and 2 cm(3) volumes were reported for bladder and rectum for each fraction. The absolute inter-fraction dose variation for each subvolume was compared using the independent sample t-test. RESULT: The mean bladder and rectal volumes, as well as the inter-fraction volume variation, were comparable for the BRSB and VGP. The BRSB resulted in a significant reduction in absolute dose as well as the inter-fraction variation for dose to 2 cm(3) rectum volumes (BRSB 0.80 Gy, standard deviation 0.71 Gy versus VGP 1.16 Gy, standard deviation 0.83 Gy; P = 0.04). Cumulative bladder D2cm(3) doses of more than 90 Gy3 were observed in six patients in the BRSB arm versus four patients in the VGP arm (P = 0.73). In both the arms, the rectal D2cm(3) doses did not exceed 75 Gy3. CONCLUSIONS: Use of a BRSB resulted in a significant reduction in inter-fraction variation in D2cm(3) rectal dose. However, no significant difference in the inter-fraction dose variation for the other subvolumes of bladder and rectum could be shown between the BRSB and VGP. The use of a BRSB may enable rectal dose reduction and inter-fraction variation where anaesthesia is not routinely used or where there is limited physician expertise. The modification suggested in the BRSB may facilitate its additional usage.

Dosimetric evaluation and clinical outcome in post-operative patients of carcinoma vulva treated with intensity-modulated radiotherapy.

BACKGROUND: To compare dosimetric parameters of intensity-modulated radiation therapy (IMRT) with 3D conformal radiotherapy (3DCRT) in post-operative patients of vulvar cancer and to assess clinical outcome and toxicity with IMRT. MATERIALS AND METHODS: A total of 8 post-operative patients of vulvar cancer were treated with IMRT. All patients were also planned by 3DCRT for comparison with IMRT. The two plans were compared in terms of conformity index, homogeneity index, tumor control probability (TCP) and normal tissue complication probability (NTCP) for the planning target volume and organs at risk (OAR). RESULTS: IMRT resulted in significantly lesser doses to rectum, bladder, bowel and femoral head as compared with 3DCRT plans. Mean conformity and homogeneity indices were better and within range with IMRT. The TCP was comparable between the two treatment plans and NTCP for rectum, bladder, bowel and femoral head was significantly less with IMRT as compared with 3DCRT. Treatment was well-tolerated and none of the patients developed Grade 3 or higher toxicity. CONCLUSION: IMRT yielded superior plans with respect to target coverage, homogeneity and conformality while lowering dose to adjacent OAR as compared with 3DCRT. Thus, IMRT offers a reduction in NTCP while maintaining TCP.

Therapeutic potential of agomelatine in epilepsy and epileptic complications.

Epilepsy is a chronic neurologic disorder which often induces numerous adverse long-term neurologic effects, such as behavioral and cognitive deficits, increased predisposition to additional seizures, and cell injury or death. Cognitive dysfunction, depression, anxiety and sleep disorders are some of the highly prevalent and most disabling complications of epilepsy. The mechanisms that lead to the generation of epileptic comorbidities are poorly understood. Treatment for epileptic complications still remains a challenge because of the poor adherence and drug interactions associated with multi drug prescriptions and also for the fear of worsening seizures by the individual medications for complications. Melatonin, an endogenous hormone secreted by pineal gland has a prominent role in epilepsy. Agomelatine is a novel antidepressant which acts as melatonin MT1 and MT2 receptor agonist and serotonin 5Ht2C receptor antagonist. The combined action at MT1/2 and 5HT2C receptors, reduction in the depolarization-evoked release of glutamate, strong neuroprotective action and possible antioxidant properties of agomelatine could make it a potential agent in the treatment of epilepsy. The effect of agomelatine on hippocampal neuronal cell survival and neurogenesis, neuroprotective effect in hippocampus and frontal cortex and the antioxidant potential may contribute to the protective action of agomelatine against epilepsy induced memory decline. Agomelatine is proven to be an antidepressant and it has relieved anxiety symptoms and improved the quality of sleep in patients with depressive disorder. The action of agomelatine as a melatonin agonist and the consequent circadian resynchronizing property as well as its action as 5-HT2C receptor antagonist, could possibly suggest an antidepressant and anxiolytic action of agomelatine in epilepsy induced depressive behavior and anxiety. Since one of the many causes of sleep disruption in epilepsy is circadian rhythm disturbances and sleep promoting and circadian effects of melatonin is attributed to the MT1 and MT2 subtypes of human melatonin receptors, agomelatine may also have a promising effect on epilepsy induced sleep disruptions. Thus with all these potential pharmacological actions, agomelatine could be recommended as a potential drug to treat epilepsy and its complications.

Dose escalation by intensity-modulated radiotherapy boost after whole pelvic radiotherapy in postoperative patients of carcinoma cervix with residual disease.

AIMS: External beam radiotherapy followed by brachytherapy is the standard treatment for patients with carcinoma cervix. However, for patients who come from peripheral hospitals after incomplete surgery, whole pelvic radiotherapy (WPRT) followed by boost with either vaginal vault brachytherapy if suitable or further external beam radiotherapy is recommended. This study was conducted to evaluate if it was possible to give a higher tumour dose using intensity-modulated radiotherapy for that group of patients who were not suitable for high dose rate vaginal vault brachytherapy because of gross disease after WPRT. MATERIALS AND METHODS: A prospective study was carried out from 2005 to 2010 in which 25 postoperative patients of cervical carcinoma with gross residual disease after WPRT of 46 Gy/23 fractions/4.5 weeks were included. Nine patients were treated with 20 Gy to the planning target volume and 30 Gy to the clinical target volume in 10 fractions; 16 patients were treated with 30 Gy to the planning target volume and 35 Gy to the clinical target volume in 15 fractions. The end points of this study were local control, survival and treatment-related toxicity. RESULTS: The median follow-up was 38 months. The 3 year local control, progression-free survival and overall survival rates were 76, 74 and 67%, respectively. Late grade 2 rectal toxicity was seen in 11 patients. Grade 2 bladder toxicity occurred in two patients and grade 3 bowel toxicity in two patients. No other grade 3 or higher toxicity was seen. CONCLUSION: Inadequate and inappropriate surgery in invasive cervical cancer with resulting gross residual disease is common in India. It is possible to escalate the tumour dose by intensity-modulated radiotherapy boost after WPRT in postoperative cervical carcinoma patients with gross residual disease with low incidence of severe toxicity and excellent local control.

Elevated land runoff after European settlement perturbs persistent foraminiferal assemblages on the Great Barrier Reef.

Coral reefs are under pressure from a variety of human-induced disturbances, but demonstration of ecosystem changes and identification of stressors are often difficult. We tested whether global change or increased agricultural runoff after European settlement of Northeast Australia (ca. 1860) has affected inshore reefs of the Great Barrier Reef. Eleven sediment cores were retrieved from inner reefs, intermediate reefs, and outer-island reefs, and benthic foraminiferal assemblages were analyzed in dated (14C, 210Pb, 137Cs) core sections (N = 82 samples). Data were grouped into six age bands (< 55, 55-150, 150-500, 500-1000, 1000-1500, and > 1500 yr). Principal component analysis and two-factor (Zone and Age) permutational analysis of variance (PERMANOVA) suggested that assemblages from the three zones were significantly different from each other over several millennia, with symbiont-bearing (mixotrophic) species dominating the outer reefs. A significant interaction term indicated that within-zone patterns varied. Assemblages in outer reefs unaffected from increased land runoff were persistent until present times. In both other zones, assemblages were also persistent until 150 yr ago, suggesting that benthic foraminiferal assemblages are naturally highly persistent over long (> 2000 yr) timescales. Assemblages in core sections < 55 yr old from inner reefs were significantly (post hoc t test) different from those older than 150 yr. Similarly, assemblages < 55 yr old from intermediate reefs were significantly different compared to older assemblages. A multivariate regression tree (environmental variables: Zone and Age) explained 56.8% of the variance in foraminiferal assemblages and confirmed patterns identified by PERMANOVA. With some exceptions, changes on the inner and intermediate reefs were consistent with a model predicting that increased nutrients and higher turbidity enhance relative abundance of heterotrophic species. Given that assemblages did not change in outer-island reefs (not impacted by runoff) we argue that changes in assemblages due to global change can be rejected as an explanation. Thus, the findings are more consistent with the hypothesis that agricultural runoff since European settlement altered foraminiferal assemblages than with the hypothesis that global forcing caused changes.

Can point doses predict volumetric dose to rectum and bladder: a CT-based planning study in high dose rate intracavitary brachytherapy of cervical carcinoma?

OBJECTIVE: Point doses, as defined by the International Commission on Radiation Units and Measurements (ICRU), are classically used to evaluate doses to the rectum and bladder in high dose rate intracavitary brachytherapy (HDR-ICBT) in cervical cancer. Several studies have shown good correlation between the ICRU point doses and the volumetric doses to these organs. In the present study we attempted to evaluate whether this correlation could be used to predict the volumetric doses to these organs. METHODS: A total of 150 HDR-ICBT insertions performed between December 2006 and June 2008 were randomly divided into two groups. Group A (n=50) was used to derive the correlation between the point and volumetric doses using regression analysis. This was tested in Group B (n=100) insertions using studentised residuals and Bland-Altman plots. RESULTS: Significant correlations were obtained for all volumetric doses and ICRU point doses for rectum and bladder in Group A insertions. The strongest correlation was found for the dose to 2 cc volumes (D(2cc)). The correlation coefficients for bladder and rectal D(2cc) versus the respective ICRU point doses were 0.82 and 0.77, respectively (p<0.001). Statistical validation of equations generated in Group B showed mean studentised residual values of 0.001 and 0.000 for the bladder and rectum. However, Bland-Altman analysis showed that the error range for these equations for bladder and rectum were ±64% and ±41% of the point A dose, respectively, which makes these equations unreliable for clinical use. CONCLUSION: Volumetric imaging is essential to obtain proper information about volumetric doses.

Quadruple malignancy in a single patient: a case report and comprehensive review of literature.

The occurrence of multiple primary malignant neoplasias (MPMN) is a rare but increasingly frequently reported event. Many theories have been proposed to explain MPMNs, but none have been proven. The key risk factors appear to be smoking and family history. While numerous studies have been published on the development of second malignancies following a first primary, the literature contains only few case reports and reviews of patients with three or more malignancies. We report a case of a young female who, over a period of 30 years, developed four different malignancies and was treated radically on each occasion.

Advanced germ cell malignancies of the ovary: should neo-adjuvant chemotherapy be the first line of treatment?

Malignant germ cell tumours of the ovary, though classically known for 'young age' and 'early stage' at presentation, are not uncommonly identified at advanced stages. Little is available in literature on the role of neo-adjuvant chemotherapy (NACT) in this group of tumours. Two patients with advanced stage ovarian germ cell tumours, including one with 45XO/46XY chromosomal mosaicism, were treated at our Institute with neo-adjuvant chemotherapy with Bleomycin, Etoposide and Cisplatin followed by surgery. Besides marked clinical improvement, intraoperatively both the patients presented no difficulty otherwise expected with widespread tumours, and histopathology report revealed no evidence of viable tumour. The article discusses the experience and suggested course of management of these tumours with NACT, which could be offered to patients with advanced malignancy in whom high surgical morbidity is anticipated or in whom only an operative biopsy was performed at laparatomy. Behaviour and management guidelines of dysgenetic gonads with XY mosaicism have also been discussed.

Carbon copy deaths: carbon monoxide gas chamber.

The news media can exert a powerful influence over suicidal behaviour. It has been observed that like-minded individuals are able to preplan a group suicide method using modern communication technology in the form of websites and online chatrooms and mobile phone texting. A case of carbon monoxide (CO) poisoning is presented to illustrate the recent phenomenon of cyber suicides by suffocation from a burning barbecue (charcoal burner) in 'gas chamber' conversions. Although barbecues (BBQ) are very popular in Britain and widely available, there have been relatively few reported cases of copycat deaths from CO gas suffocation.